Development of miniaturized (micro) total analysis systems (μTAS) is of increasing interest in the biomedical research community. Often referred to as ‘Laboratory-on-a-chip’ (or LOC), this technology offers new prospects for health care delivery and biomedical research. Envisioned are microsystems for massively parallel chemical analysis, drug testing, bioassay, and diagnostic devices for non-invasive, early detection of cancers and other serious health problems.
Real biological cells, such as erythrocytes, cells derived from tissue, and microbial cells express a high degree of heterogeneity in a typical population. When subjected to nonuniform electrical fields, individual cells in these populations manifest a wide range of AC electrokinetic responses and behaviors [1-3]. References indicated by numerals in square brackets are listed at the end of the disclosure and incorporated by reference herein. Furthermore, these characteristic dielectric fingerprints are quite sensitive to the sample environment. Specifically, the frequency-dependent polarization response reflected in the dielectrophoretic (DEP), electrorotation (ROT) and traveling wave dielectrophoresis (TW-DEP) spectra of viable, nonviable and/or diseased cells manifest highly distinguishable characteristics in certain regions of the frequency spectrum.
In the past, cellular DEP has been practiced primarily using closed fluidic chambers or interconnected microchannels interfaced to external fluid pumping and sample injection hardware [2, 4]. Such systems, particularly those employing microfluidic channels for cell collection and separation, usually require sample preprocessing and are often plagued by micro-channel blockage. By their very nature, closed channel microfluidic systems are very complex structures, requiring extensive on-chip valving and flow control devices. The pressure differentials required to force liquids through the narrow channels are sufficiently high (˜105 Pa) are high enough so that leakage becomes a concern. For successful commercialization in microfluidic cell analysis/sorting devices, these problems must be overcome.
An attractive alternative to the closed channel microfluidic systems is open-channel microfluidics for micro and potentially nanoscale DEP-actuated fluidic transport and subsequent particle manipulation [5, 6]. In the preferred embodiment of such open systems, droplets themselves serve as the carriers for the cells or biological molecules and the reagents needed for biochemical protocols. Because the liquid samples are sessile droplets residing on an open substrate, such systems are immune to microchannel blockage. The basic design rules for DEP droplet dispensing have been published in two papers [10, 11]. King et al. showed that particles can be transported using transient liquid DEP actuation [12] with sorting based on particle size. The present application addresses a novel approach for particle sorting that builds upon DEP actuated liquid transport.